The glutamate/glycine NMDA receptor has been implicated in a variety of central nervous system disorders and pathological conditions. In particular, NMDA receptor hypofunction appears to contribute significantly to schizophrenia and cognitive deficits. In the following application, a research program is described that is aimed at identifying novel drug candidates, for potentiating NMDA receptor activity. We have discovered prototype compounds, and further assay development and compound screening is proposed in this Phase I application. Novel molecules, which increase NMDA receptor function, have considerable commercial potential for the treatment of schizophrenia and of dementias such as Alzheimer's disease. PROPOSED COMMERCIAL APPLICATIONS: Compounds identified through the studies outlined in this proposal will have the potential for the treatment of schizophrenia and dementias such as Alzheimer's disease.